Drugs approved with limited data aren’t always well-tested later

(Reuters Health) - New medicines that win U.S. marketing approval
without conclusive evidence of their effectiveness aren't always
proven to work after they go on sale, a recent research review
suggests.

Researchers focused on medicines approved for sale based on
single pivotal trials or based on what's known as "surrogate
markers," such as lab tests and signs of risk for disease such as
cholesterol levels instead of true clinical outcomes like heart
attacks or deaths. Many times no follow-up studies were published
after these medicines went on sale, and when studies were
published they often continued to rely on surrogate markers to
suggest potential effectiveness.

"Everyone wants new drugs to be approved for use as quickly as
possible - patients want access to innovative therapies and
physicians want alternatives for their patients, particularly if
they work better or are safer," said senior study author Dr.
Joseph Ross of Yale University in New Haven, Connecticut.

"However, speeding up the approval process increases our
collective uncertainty about drugs' benefits and safety," Ross
said by email. "This exposes patients to risks - the risk that
they are spending their resources on therapies that do not work
as well as expected as well as the possibility that they are
taking drugs that have underlying safety risks that have not yet
been figured out."

For the study, researchers examined published studies of 117
medicines approved for treating 123 medical conditions by the
U.S. Food and Drug Administration between 2005 and 2012, based on
either a single pivotal trial or on trials that relied on
surrogate endpoints.

Overall, no follow-up studies were published for 43 of the 123
approved indications, or 35 percent, researchers report in the
BMJ. They examined research published up to about five years
after the drugs won FDA approval.

For half of the conditions, no more than one post-approval study
was published, the researchers found.

For the medicines cleared for sale based on surrogate markers, 90
percent of the studies published after they went on sale also
used surrogate markers of disease.

Only six of the 33 uses for the drugs that had been approved by
the FDA based on a single pivotal trial had a study published
after approval that was a random experiment and proved the
medicine worked better for specific clinical outcomes than a
placebo or an alternative therapy.

Just one of the 49 uses approved based only on studies of
surrogate markers had a gold-standard randomized study of
clinical outcomes published after it went on sale that proved it
worked better than no treatment or alternatives.

And only two of the 41 uses approved with a single pivotal trial
and surrogate markers had a randomized study proving superior
clinical effectiveness published after it was cleared for sale.

It's possible that studies published after the analysis was done
might have proven some of the medicines worked better than
alternatives for specific clinical outcomes, the authors note.
The results might also look different for other medicines that
were approved with multiple pivotal trials instead of with only
one, they say.

Even so, The study should make patients cautious about whether
they are benefiting from new medicines before the health effects
of the drugs are fully understood, said Dr. Barbara Mintzes, a
researcher at the University of Sydney who wasn't involved in the
study.

"This study raised a strong note of caution because the follow-up
studies needed to show if these medicines are truly beneficial
are either not being done or do not use the type of rigorous
scientific methods needed to adequately test these medicines,"
Mintzes said by email. "In many cases, when a new medicine is
approved, there are already better tested treatments available."

SOURCE: http://bit.ly/2qzRHzC BMJ, online May 3, 2017.

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